Registration of low-SNR high-resolution diffusion-weighted images

This paper introduces a novel, high-speed scheme for intrasubject registration and segmentation of high-resolution multi-shot diffusion-weighted images. Compared to single-shot sequences, multi-shot have advantages in terms of improved spatial resolution and reduced eddy-current and susceptibility artifacts. However, these sequences have prolonged scan times increasing the risk of subject motion, and, a lower signal to noise ratio (SNR) with smaller voxel volumes. The proposed registration algorithm comprises a hybrid thresholding expectation-maximization segmentation method that can cope with the low-SNR, and registers diffusion-weighted to B0 images through fast detection and matching of features found in edge images derived from floating and reference images. We performed validations of the entire pipeline, including assessment of visual appearance by experts, consistency error computations, and analysis of the segmentation, using volunteer images, and found its performance to be comparable with, or exceeding, that of established solutions

Technologies for Biomechanically-Informed Image Guidance of Laparoscopic Liver Surgery

Laparoscopic surgery for liver resection has a number medical advantages over open surgery, but also comes with inherent technical challenges. The surgeon only has a very limited field of view through the imaging modalities routinely employed intra-operatively, laparoscopic video and ultrasound, and the pneumoperitoneum required to create the operating space and gaining access to the organ can significantly deform and displace the liver from its pre-operative configuration. This can make relating what is visible intra-operatively to the pre-operative plan and inferring the location of sub-surface anatomy a very challenging task. Image guidance systems can help overcome these challenges by updating the pre-operative plan to the situation in theatre and visualising it in relation to the position of surgical instruments. In this thesis, I present a series of contributions to a biomechanically-informed image-guidance system made during my PhD. The most recent one is work on a pipeline for the estimation of the post-insufflation configuration of the liver by means of an algorithm that uses a database of segmented training images of patient abdomens where the post-insufflation configuration of the liver is known. The pipeline comprises an algorithm for inter and intra-subject registration of liver meshes by means of non-rigid spectral point-correspondence finding. My other contributions are more fundamental and less application specific, and are all contained and made available to the public in the NiftySim open-source finite element modelling package. Two of my contributions to NiftySim are of particular interest with regards to image guidance of laparoscopic liver surgery: 1) a novel general purpose contact modelling algorithm that can be used to simulate contact interactions between, e.g., the liver and surrounding anatomy; 2) membrane and shell elements that can be used to, e.g., simulate the Glisson capsule that has been shown to significantly influence the organ’s measured stiffness

Image-driven Stochastic Identification of Boundary Conditions for Predictive Simulation

International audienceIn computer-aided interventions, biomechanical models reconstructed from the pre-operative data are used via augmented reality to facilitate the intra-operative navigation. The predictive power of such models highly depends on the knowledge of boundary conditions. However , in the context of patient-specific modeling, neither the pre-operative nor the intra-operative modalities provide a reliable information about the location and mechanical properties of the organ attachments. We present a novel image-driven method for fast identification of boundary conditions which are modelled as stochastic parameters. The method employs the reduced-order unscented Kalman filter to transform in real-time the probability distributions of the parameters, given observations extracted from intra-operative images. The method is evaluated using synthetic, phantom and real data acquired in vivo on a porcine liver. A quantitative assessment is presented and it is shown that the method significantly increases the predictive power of the biomechanical model

Explicit Contact Modelling for Surgical Computer Guidance and Simulation

Realistic modelling of mechanical interactions between tissues is an important part of surgical simulation, and may become a valuable asset in surgical computer guidance. Unfortunately, it is also computationally very demanding. Explicit matrix-free FEM solvers have been shown to be a good choice for fast tissue simulation, however little work has been done on contact algorithms for such FEM solvers. This work introduces such an algorithm that is capable of handling both deformable-deformable (soft-tissue interacting with soft-tissue) and deformable-rigid (e.g. soft-tissue interacting with surgical instruments) contacts. The proposed algorithm employs responses computed with a fully matrix-free, virtual node-based version of the model first used by Taylor and Flanagan in PRONTO3D. For contact detection, a bounding-volume hierarchy (BVH) capable of identifying self collisions is introduced. The proposed BVH generation and update strategies comprise novel heuristics to minimise the number of bounding volumes visited in hierarchy update and collision detection. Aside from speed, stability was a major objective in the development of the algorithm, hence a novel method for computation of response forces from C0-continuous normals, and a gradual application of response forces from rate constraints has been devised and incorporated in the scheme. The continuity of the surface normals has advantages particularly in applications such as sliding over irregular surfaces, which occurs, e.g., in simulated breathing. The effectiveness of the scheme is demonstrated on a number of meshes derived from medical image data and artificial test cases

Database-Based Estimation of Liver Deformation under Pneumoperitoneum for Surgical Image-Guidance and Simulation

The insufflation of the abdomen in laparoscopic liver surgery leads to significant deformation of the liver. The estimation of the shape and position of the liver after insufflation has many important applications, such as providing surface-based registration algorithms used in image guidance with an initial guess and realistic patient-specific surgical simulation. Our proposed algorithm computes a deformation estimate for a patient subject from a database of known insufflation deformations, as a weighted average. The database is built from pre-operative and intra-operative 3D image segmentations. The estimation pipeline also comprises a biomechanical simulation to incorporate patient-specific boundary conditions (BCs) and eliminate any non-physical deformation arising from the computation of the deformation as a weighted average. We have evaluated the accuracy of our intra-subject registration, used for the computation of the displacements stored in the database, and our liver deformation predictions based on segmented, in-vivo porcine CT image data from 5 animals and manually selected vascular landmarks. We found root mean squared (RMS) target registration errors (TREs) of 2.96-11.31mm after intra-subject registration. For our estimated deformation, we found an RMS TRE of 5.82-11.47mm for four of the subjects, on one outlier subject the method failed

TIEG1/KLF10 Modulates Runx2 Expression and Activity in Osteoblasts

Deletion of TIEG1/KLF10 in mice results in a gender specific osteopenic skeletal phenotype with significant defects in both cortical and trabecular bone, which are observed only in female animals. Calvarial osteoblasts isolated from TIEG1 knockout (KO) mice display reduced expression levels of multiple bone related genes, including Runx2, and exhibit significant delays in their mineralization rates relative to wildtype controls. These data suggest that TIEG1 plays an important role in regulating Runx2 expression in bone and that decreased Runx2 expression in TIEG1 KO mice is in part responsible for the observed osteopenic phenotype. In this manuscript, data is presented demonstrating that over-expression of TIEG1 results in increased expression of Runx2 while repression of TIEG1 results in suppression of Runx2. Transient transfection and chromatin immunoprecipitation assays reveal that TIEG1 directly binds to and activates the Runx2 promoter. The zinc finger containing domain of TIEG1 is necessary for this regulation supporting that activation occurs through direct DNA binding. A role for the ubiquitin/proteasome pathway in fine tuning the regulation of Runx2 expression by TIEG1 is also implicated in this study. Additionally, the regulation of Runx2 expression by cytokines such as TGFβ1 and BMP2 is shown to be inhibited in the absence of TIEG1. Co-immunoprecipitation and co-localization assays indicate that TIEG1 protein associates with Runx2 protein resulting in co-activation of Runx2 transcriptional activity. Lastly, Runx2 adenoviral infection of TIEG1 KO calvarial osteoblasts leads to increased expression of Runx2 and enhancement of their ability to differentiate and mineralize in culture. Taken together, these data implicate an important role for TIEG1 in regulating the expression and activity of Runx2 in osteoblasts and suggest that decreased expression of Runx2 in TIEG1 KO mice contributes to the observed osteopenic bone phenotype

Evaluating comorbidities in total hip and knee arthroplasty: available instruments

Each year millions of patients are treated for joint pain with total joint arthroplasty, and the numbers are expected to rise. Comorbid disease is known to influence the outcome of total joint arthroplasty, and its documentation is therefore of utmost importance in clinical evaluation of the individual patient as well as in research. In this paper, we examine the various methods for obtaining and assessing comorbidity information for patients undergoing joint replacement. Multiple instruments are reliable and validated for this purpose, such as the Charlson Index, Index of Coexistent Disease, and the Functional Comorbidity Index. In orthopedic studies, the Charnley classification and the American Society of Anesthesiologists physical function score (ASA) are widely used. We recommend that a well-documented comorbidity index that incorporates some aspect of mental health is used along with other appropriate instruments to objectively assess the preoperative status of the patient

Novel Insights into the Diversity of Catabolic Metabolism from Ten Haloarchaeal Genomes

BACKGROUND: The extremely halophilic archaea are present worldwide in saline environments and have important biotechnological applications. Ten complete genomes of haloarchaea are now available, providing an opportunity for comparative analysis. METHODOLOGY/PRINCIPAL FINDINGS: We report here the comparative analysis of five newly sequenced haloarchaeal genomes with five previously published ones. Whole genome trees based on protein sequences provide strong support for deep relationships between the ten organisms. Using a soft clustering approach, we identified 887 protein clusters present in all halophiles. Of these core clusters, 112 are not found in any other archaea and therefore constitute the haloarchaeal signature. Four of the halophiles were isolated from water, and four were isolated from soil or sediment. Although there are few habitat-specific clusters, the soil/sediment halophiles tend to have greater capacity for polysaccharide degradation, siderophore synthesis, and cell wall modification. Halorhabdus utahensis and Haloterrigena turkmenica encode over forty glycosyl hydrolases each, and may be capable of breaking down naturally occurring complex carbohydrates. H. utahensis is specialized for growth on carbohydrates and has few amino acid degradation pathways. It uses the non-oxidative pentose phosphate pathway instead of the oxidative pathway, giving it more flexibility in the metabolism of pentoses. CONCLUSIONS: These new genomes expand our understanding of haloarchaeal catabolic pathways, providing a basis for further experimental analysis, especially with regard to carbohydrate metabolism. Halophilic glycosyl hydrolases for use in biofuel production are more likely to be found in halophiles isolated from soil or sediment